Phosphomonoesterases of Schistosoma mansoni

Nimmo-Smith, R. H.; Standen, O. D.

doi:10.1016/0014-4894(63)90082-1

Cited by 71 publications

(21 citation statements)

References 39 publications

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“…The 8renter activity of acid phosphatase in G. tigrinum agrees with the observations of earlier investigators Pennoit-De cooman and van Grembergen (1942) in Fasciola hepatica, Ma (1964) in Clonorchis sinensis, Goil (1966) in Gastrathylax crumentfer, Halton (1967) in Haematoloechus medioplexus, Haplometra cylindracea, Opisthioglyphe ranae, Diplodiscus subclavatus, Gorgoderina vitelliloba, Gorgodera cygnoides, Fasciola hepatica and Schistosoma mansoni, Probert, Goil and Sharma (1972) in Fasciola gigantica, Lwia (1974) in F. hepatica andNimmo-Smith andStanden (1963) in Schistosoma mansoni. It is therefore evident that a high level of acid phosphatase exists in all the adult trematodes so far studied.…”

Section: Discussionsupporting

confidence: 80%

Non-specific phosphomonoesterases ofGaneo tigrinum Mehra and Negi, 1928 (Trematoda)

Sathyanarayana

Anantaraman

1979

Proc. Indian Acad. Sci.

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Section: Discussionsupporting

confidence: 80%

Non-specific phosphomonoesterases ofGaneo tigrinum Mehra and Negi, 1928 (Trematoda)

Sathyanarayana

Anantaraman

1979

Proc. Indian Acad. Sci.

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“…Early work revealed alkaline phosphatase activity in the parasite surface membranes ( 44 , 45 ) and, almost certainly, the activity of SmAP was being measured. More recent tegument proteomic studies ( 46 – 48 ), as well as immunolocalization experiments ( 16 , 17 ), confirm that SmAP is found in the parasite surface membranes.…”

Section: Discussionmentioning

confidence: 99%

Intravascular Schistosoma mansoni Cleave the Host Immune and Hemostatic Signaling Molecule Sphingosine-1-Phosphate via Tegumental Alkaline Phosphatase

et al. 2018

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Schistosomes are parasitic flatworms that infect the vasculature of >200 million people around the world. These long-lived parasites do not appear to provoke blood clot formation or obvious inflammation around them in vivo. Proteins expressed at the host–parasite interface (such as Schistosoma mansoni alkaline phosphatase, SmAP) are likely key to these abilities. SmAP is a glycoprotein that hydrolyses the artificial substrate p-nitrophenyl phosphate in a reaction that requires Mg2+ and at an optimal pH of 9. SmAP additionally cleaves the nucleoside monophosphates AMP, CMP, GMP, and TMP, all with a similar Km (~600–650 μM). Living adult worms, incubated in murine plasma for 1 h, alter the plasma metabolome; a decrease in sphingosine-1-phosphate (S1P) is accompanied by an increase in the levels of its component parts—sphingosine and phosphate. To test the hypothesis that schistosomes can hydrolyze S1P (and not merely recruit or activate a host plasma enzyme with this function), living intravascular life-stage parasites were incubated with commercially obtained S1P and cleavage of S1P was detected. Parasites whose SmAP gene was suppressed using RNAi were impaired in their ability to cleave S1P compared to controls. In addition, recombinant SmAP hydrolyzed S1P. Since extracellular S1P plays key roles in controlling inflammation and platelet aggregation, we hypothesize that schistosome SmAP, by degrading S1P, can regulate the level of this bioactive lipid in the environment of the parasites to control these processes in the worm’s local environment. This is the first report of any parasite being able to cleave S1P.

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“…These activities in schistosomes are correlated with activities towards β-glycerophosphate (Table 2) indicating that the dephosphorylation of pyrimidine nucleoside 5′-monophosphates in schistosomes are due to alkaline phosphatases rather than the more specific 5′-nucleotidases (EC 3.1.3.5) (Nimmo-Smith and Standen, 1963; Levy and Read, 1975a and 1975b; Cesari et al, 1981; el Kouni and Naguib, 1990). These activities are associated with the particulate fraction of the parasite which is constituted mainly of the tegument of the parasite (Nimmo-Smith and Standen, 1963; Levy and Read, 1975a and 1975b; Wheater and Wilson, 1976; Ernst, 1976; Simpson et al, 1981; Cesari et al, 1981; el Kouni and Naguib, 1990). The tegument of the adult schistosome is delimited by a double membrane that completely surrounds the parasite (Hockley and McLaren, 1973).…”

Section: Enzymes Of Pyrimidine Salvage Pathwaysmentioning

confidence: 97%

“…Extracts of adult Schistosoma mansoni have high levels of phosphatase activities capable of dephosphorylating pyrimidine nucleoside 5′-monophosphates (Nimmo-Smith and Standen, 1963; Levy and Read, 1975a and 1975b; Cesari et al, 1981; el Kouni and Naguib, 1990). These activities in schistosomes are correlated with activities towards β-glycerophosphate (Table 2) indicating that the dephosphorylation of pyrimidine nucleoside 5′-monophosphates in schistosomes are due to alkaline phosphatases rather than the more specific 5′-nucleotidases (EC 3.1.3.5) (Nimmo-Smith and Standen, 1963; Levy and Read, 1975a and 1975b; Cesari et al, 1981; el Kouni and Naguib, 1990).…”

Section: Enzymes Of Pyrimidine Salvage Pathwaysmentioning

confidence: 99%

Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

Kouni

2017

Comparative Biochemistry and Physiology Part B: Biochemistry an

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Schistosomes are responsible for the parasitic disease schistosomiasis, an acute and chronic parasitic ailment that affects more than 240 million people in 70 countries worldwide. It is the second most devastating parasitic disease after malaria. At least 200,000 deaths per year are associated with the disease. In the absence of the availability of vaccines, chemotherapy is the main stay for combating schistosomiasis. The antischistosomal arsenal is currently limited to a single drug, Praziquantel, which is quite effective with a single-day treatment and virtually no host-toxicity. Recently, however, the question of reduced activity of Praziquantel has been raised. Therefore, the search for alternative antischistosomal drugs merits the study of new approaches of chemotherapy. The rational design of a drug is usually based on biochemical and physiological differences between pathogens and host. Pyrimidine metabolism is an excellent target for such studies. Schistosomes, unlike most of the host tissues, require a very active pyrimidine metabolism for the synthesis of DNA and RNA. This is essential for the production of the enormous numbers of eggs deposited daily by the parasite to which the granulomas response precipitate the pathogenesis of schistosomiasis. Furthermore, there are sufficient differences between corresponding enzymes of pyrimidine metabolism from the host and the parasite that can be exploited to design specific inhibitors or “subversive substrates” for the parasitic enzymes. Specificities of pyrimidine transport also diverge significantly between parasites and their mammalian host. This review deals with studies on pyrimidine metabolism in schistosomes and highlights the unique characteristic of this metabolism that could constitute excellent potential targets for the design of safe and effective antischistosomal drugs. In addition, pyrimidine metabolism in schistosomes is compared with that in other parasites where studies on pyrimidine metabolism have been more elaborate, in the hope of providing leads on how to identify likely chemotherapeutic targets which have not been looked at in schistosomes.

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Phosphomonoesterases of Schistosoma mansoni

Cited by 71 publications

References 39 publications

Non-specific phosphomonoesterases ofGaneo tigrinum Mehra and Negi, 1928 (Trematoda)

Non-specific phosphomonoesterases ofGaneo tigrinum Mehra and Negi, 1928 (Trematoda)

Intravascular Schistosoma mansoni Cleave the Host Immune and Hemostatic Signaling Molecule Sphingosine-1-Phosphate via Tegumental Alkaline Phosphatase

Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

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